ET-1在放射性肺损伤中的改变及维甲酸、氟伐他汀的治疗作用

目的　探讨血浆及肺组织中ET 1在放射性肺损伤中的改变及维甲酸、氟伐他汀对其治疗作用。方法　健康雌性SD大鼠 10 0只随机分为 5组 :正常对照组 (N)、单纯照射组 (S)、维甲酸治疗组 (W)、维甲酸 氟伐他汀治疗组 (L)、地塞米松治疗组 (D) ,每组 2 0只。后 4组行直线加速器全胸部照射 ,照射后次日维甲酸治疗组灌服维甲酸 ,L组灌服维甲酸、氟伐他汀 ,D组灌服地塞米松 ,于照射后 5 ,15 ,30 ,6 0d采血测定ET 1浓度 ,肺组织测定ET 1免疫组化。结果　照射后肺组织炎症和肺水肿进行性加重 ;照射后 5 ,15 ,30 ,6 0dS组血浆ET 1水平较N组进行性升高 (P <0 0 5 ) ,L组15 ,30 ,6 0d血浆ET 1水平降低 (P <0 0 5 ) ,其余各组差异无显著性。S组ET 130 ,6 0d表达增强(P <0 0 5 )。W组 30d抑制ET 1表达 (P <0 0 1) ,L组 15d抑制ET 1在肺上皮细胞、巨噬细胞 ,炎症细胞的表达 (P <0 0 1) ,30 ,6 0d时所有表达部位都出现抑制 (P <0 0 5 )。D组 6 0dET 1表达减弱。结论　血浆ET 1水平的变化能反映放射性肺损伤的严重程度 ,维甲酸、氟伐他汀能抑制肺组织ET 1的表达 ,降低血浆ET 1水平 ,可能是维甲酸、氟伐他汀治疗放射性肺损伤的一个作用机理。

Changes of endothelin-1 and curative effect of retinoic acid and fluvastatin in lung injury induced by thoracic radiation

Objective To explore the changes of endothelin-1 in plasma and lung tissues,and the curative effect of retinoic acid as well as fluvastatin in radiation lung injury. Methods Altogether 100 female SD rats were divided randomly into 5 groups:the control group (N),irradiation alone group(S),retinoic acid treatment group(W),retinoic acid and fluvastatin treatment group(L),and dexamethasone treatment group(D).Each group had 20 rats.Rats of the latter four groups were irradiated with a linear accelaretor at a dose of 20 Gy thoracically.Retinoic acid was gastrogavaged at a dose of 20 mg 5kg -1 5d {-1 } in group W on the second day after irradiation,Retinoic acid and fluvastatin were gastrogavaged each at a dose of 10 mg 5kg {-1 } 5d {-1 } in group L.Dexamethasone was gastrogavaged at a dose of 3 ^33 mg 5kg {-1 } 5d {-1 } in group D.The contents of endothelin-1 (ET-1) in plasma were measured on days 5,15,30 and 60.ET-1 was also determined in lung tissue by immunohistochemitry. Results Pulmonary edema and pneumonia aggravated gradually in group S and alleviated in group W and group L.ET-1 increased in group L significantly in plasma beginning from day 5 ( P< 0.05),and decreased on days 15,30,and 60 ( P <0.05).The expression of ET-1 in lung tissues became stronger in groups on days 30 and 60 ( P< 0.05).Retinoic acid could inhibit the expression of ET-1 on day 30 ( P< 0 ^01),Retinoic acid together with fluvastatin could inhibit the expression of ET-1 in the epithelial cells,macrophages and inflammatory cells on day 15 ( P< 0 ^05),and all expression sites were inhibited on days 30 and 60 ( P< 0 ^05).The expression of ET-1 was dim in group D on day 60. Conclusions ET-1 could reflect the degree of radiation lung injury.Retinoic and fluvastatin could inhibit expression of ET-1 in the lung tissue,and they could decrease ET-1 content in plasma significantly.This might be one of their mechanisms in treatment of radiation lung injury. ;